Associations between genetic variants near the CHREBP locus and lipoprotein concentrations may be modified by sugar-sweetened beverage consumption

Authors: HASLAM, DANIELLE - Harvard University; PELOSO, GINA - Massachusetts General Hospital; SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DUPUIS, JOSEE - Boston University; DASHTI, HASSAN - Harvard University; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; HERMAN, MARK - Duke University; MCKEOWN, NICOLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Current Developments in Nutrition
Publication Type: Abstract Only
Publication Acceptance Date: 2/18/2020
Publication Date: 5/29/2020
Citation: Haslam, D.E., Peloso, G.M., Smith, C.E., Dupuis, J., Dashti, H.S., Lichtenstein, A.H., Herman, M.A., McKeown, N.M. 2020. Associations between genetic variants near the CHREBP locus and lipoprotein concentrations may be modified by sugar-sweetened beverage consumption. Current Developments in Nutrition. 4(Suppl_2):1256. https://doi.org/10.1093/cdn/nzaa058_014.
DOI: https://doi.org/10.1093/cdn/nzaa058_014

Interpretive Summary:

Technical Abstract: Background: Genome-wide association studies (GWAS) have identified genetic determinants of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations, but these loci only account for a fraction of the estimated heritability. Carbohydrate responsive element binding protein (ChREBP) is a transcription factor that responds to sugar consumption. Consumption of sugar-sweetened beverages (SSB) and genetic variants at the CHREBP (also known as MLXIPL) locus have separately been linked to dyslipidemia. We hypothesized that SSB intake may modify the associations of CHREBP variants and HDL-C and TG concentrations. Methods: We conducted a cross-sectional analysis of data from 11 Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium cohorts (N=63,599). A total of 1,606 single-nucleotide polymorphisms (SNPs) were selected within or near the CHREBP locus. SSB consumption (sodas, fruit punches, lemonades, or other fruit drinks) was estimated from food-frequency questionnaires. Participants were grouped by category of SSB intake (<1 serving/month, 1-4 serving/month, 1-2 serving/week, 3-7 serving/week, >1 serving/day). Inverse-variance weighted fixed- and random-effect meta-analyses were used to quantify the following associations: 1) SSB consumption and HDL-C and TG concentrations; 2) selected SNPs and HDL-C and TG concentrations; and 3) interactions between SSB consumption and selected SNPs, and HDL-C and TG concentrations. Results: SSB consumption was inversely associated with HDL-C and positively associated with TG concentrations (ptrend <0.0001). We first replicated previously observed GWAS associations between one SNP on HDL-C (rs71556736) and two distinct SNPs (rs71556736 and rs13225660) on TG concentrations (Bonferroni-corrected p<0.0001). Additionally, we identified two distinct novel SNP associations with TG concentrations (rs42124 and rs10245965) in this locus. One distinct SNP displayed a statistically significant difference in effect by category of SSB consumption with HDL-C (rs71556729), and additional SNPs displayed a suggestive difference for both HDL-C and TG concentrations. Conclusions: Our results indicate that high SSB consumption may modify the association between genetic variants within or near the CHREBP locus and HDL-C and TG concentrations.